Targeting of Calbindin 1 rescues erythropoiesis in a human model of Diamond Blackfan anemia.
CALB1
CRISPR screen
DBA
Erythropoiesis
Journal
Blood cells, molecules & diseases
ISSN: 1096-0961
Titre abrégé: Blood Cells Mol Dis
Pays: United States
ID NLM: 9509932
Informations de publication
Date de publication:
09 2023
09 2023
Historique:
received:
26
04
2023
revised:
20
05
2023
accepted:
20
05
2023
pmc-release:
01
09
2024
medline:
20
6
2023
pubmed:
3
6
2023
entrez:
2
6
2023
Statut:
ppublish
Résumé
Diamond Blackfan anemia (DBA) is an inherited bone marrow failure syndrome characterized by congenital anomalies, cancer predisposition and a severe hypo-proliferative anemia. It was the first disease linked to ribosomal dysfunction and >70 % of patients have been identified to have a haploinsufficiency of a ribosomal protein (RP) gene, with RPS19 being the most common mutation. There is significant variability within the disease in terms of phenotype as well as response to therapy suggesting that other genes contribute to the pathophysiology and potential management of this disease. To explore these questions, we performed a genome-wide CRISPR screen in a cellular model of DBA and identified Calbindin 1 (CALB1), a member of the calcium-binding superfamily, as a potential modifier of the disordered erythropoiesis in DBA. We used human derived CD34+ cells cultured in erythroid stimulating media with knockdown of RPS19 as a model for DBA to study the effects of CALB1. We found that knockdown of CALB1 in this DBA model promoted erythroid maturation. We also noted effects of CALB1 knockdown on cell cycle. Taken together, our results reveal CALB1 is a novel regulator of human erythropoiesis and has implications for using CALB1 as a novel therapeutic target in DBA.
Identifiants
pubmed: 37267698
pii: S1079-9796(23)00036-0
doi: 10.1016/j.bcmd.2023.102759
pmc: PMC10330851
mid: NIHMS1906661
pii:
doi:
Substances chimiques
Calbindin 1
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
102759Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL144436
Pays : United States
Informations de copyright
Copyright © 2023 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest None.
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